Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Mehta, Ishita; Amira, Manelle; Harvey, Amanda; Bridger, Joanna M.

doi:10.1186/gb-2010-11-1-r5

Cited by 167 publications

(217 citation statements)

References 68 publications

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“…7). This observation is in contrast to the dynamic changes in nuclear organization observed under stress response conditions (13,30,31), in which loci move in less time than is required for a cell cycle. The nuclear topology did not return to its prestress configuration until after release from a mitotic block, however (30).…”

Section: Discussioncontrasting

confidence: 52%

“…S9). Previous investigators have suggested that mitosis is necessary for the repositioning of genes during differentiation (7,30,31,51). Our chimeric myotube strategy allowed us to directly test whether changes in lineage-specific nuclear topology are dependent on cell division.…”

Section: Cell Division Is Required For Establishing Changes In Nucleamentioning

confidence: 99%

“…Specific genes, generally those involved in a rapid cellular response to a stimulus such as stress, can dynamically change positions (13), and these changes can alter CT positioning (30,31); however, interphase chromatin demonstrates constrained diffusion for the most part, consistent with the Brownian motion of an object tethered in space (32,33). During mitosis, the relationship between gene expression and organization is lost on dissolution of the nucleus (34).…”

Section: Significancementioning

confidence: 99%

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Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

Neems

Garza-Gongora

Smith

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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The linear distribution of genes across chromosomes and the spatial localization of genes within the nucleus are related to their transcriptional regulation. The mechanistic consequences of linear gene order, and how it may relate to the functional output of genome organization, remain to be fully resolved, however. Here we tested the relationship between linear and 3D organization of gene regulation during myogenesis. Our analysis has identified a subset of topologically associated domains (TADs) that are significantly enriched for muscle-specific genes. These lineage-enriched TADs demonstrate an expression-dependent pattern of nuclear organization that influences the positioning of adjacent nonenriched TADs. Therefore, lineageenriched TADs inform cell-specific genome organization during myogenesis. The reduction of allelic spatial distance of one of these domains, which contains Myogenin, correlates with reduced transcriptional variability, identifying a potential role for lineage-specific nuclear topology. Using a fusion-based strategy to decouple mitosis and myotube formation, we demonstrate that the cell-specific topology of syncytial nuclei is dependent on cell division. We propose that the effects of linear and spatial organization of gene loci on gene regulation are linked through TAD architecture, and that mitosis is critical for establishing nuclear topologies during cellular differentiation.cell differentiation | gene regulation | nuclear organization | transcriptional noise | 3D image analysis

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Section: Discussioncontrasting

confidence: 52%

Section: Cell Division Is Required For Establishing Changes In Nucleamentioning

confidence: 99%

Section: Significancementioning

confidence: 99%

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Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

Neems

Garza-Gongora

Smith

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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“…It is therefore plausible that these biochemical properties of actin are utilized also within the nucleus. Indeed, actin and nuclear myosins have been implicated in the movement of individual gene loci upon transcription activation (14)(15)(16) and even in rearranging whole chromosomes within the nucleus (17). Furthermore, although the functional conformation of nuclear actin is still under debate (18,19), many of the nuclear actin related functions mentioned above are disrupted upon treatment of cells with drugs affecting actin polymerization (15,20,21), suggesting that actin polymerization plays a role also in the cell nucleus.…”

mentioning

confidence: 99%

Active maintenance of nuclear actin by importin 9 supports transcription

Dopie

Skarp

Rajakylä

et al. 2012

Proc. Natl. Acad. Sci. U.S.A.

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Besides its essential and well established role as a component of the cytoskeleton, actin is also present in the cell nucleus, where it has been linked to many processes that control gene expression. For example, nuclear actin regulates the activity of specific transcription factors, associates with all three RNA polymerases, and is a component of many chromatin remodelling complexes. Despite the fact that two export receptors, Crm1 and exportin 6, have been linked to nuclear export of actin, the mechanism by which actin enters the nucleus to elicit these essential functions has not been determined. It is also unclear whether actin is actively exchanged between the nucleus and the cytoplasm, and whether this connection has any functional significance for the cell. By applying a variety of live-cell imaging techniques we revealed that actin constantly shuttles in and out of the nucleus. The fast transport rates, which depend on the availability of actin monomers, suggest an active transport mechanism in both directions. Importantly, we identified importin 9 as the nuclear import factor for actin. Furthermore, our RNAi experiments showed that the active maintenance of nuclear actin levels by importin 9 is required for maximal transcriptional activity. Measurements of nuclear export rates and depletion studies also clarified that nuclear export of actin is mediated by exportin 6, and not by Crm1. These results demonstrate that cytoplasmic and nuclear actin pools are dynamically connected and identify the nuclear import and export mechanisms of actin.

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“…Furthermore, radial positioning suggests that there might be a quantitative relationship between CT's gene density and CT's distance to nuclear center, according to the "spherical 1 Mb chromatin domain" model [29]. However, gene-poor chromosomes can move away from nuclear periphery in quiescent or senescent human fibroblasts [30,31].…”

Section: Models For Interphase Chromosome Positioningmentioning

confidence: 99%

Developing bioimaging and quantitative methods to study 3D genome

et al. 2016

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The recent advances in chromosome configuration capture (3C)-based series molecular methods and optical superresolution (SR) techniques offer powerful tools to investigate three dimensional (3D) genomic structure in prokaryotic and eukaryotic cell nucleus. In this review, we focus on the progress during the last decade in this exciting field. Here we at first introduce briefly genome organization at chromosome, domain and sub-domain level, respectively; then we provide a short introduction to various super-resolution microscopy techniques which can be employed to detect genome 3D structure. We also reviewed the progress of quantitative and visualization tools to evaluate and visualize chromatin interactions in 3D genome derived from Hi-C data. We end up with the discussion that imaging methods and 3C-based molecular methods are not mutually exclusive ----actually they are complemental to each other and can be combined together to study 3D genome organization.Keywords: 3D Genome; quantitative methods; bioimaging; super resolution INTRODUCTIONIn eukaryotic nucleus, the organization of chromatin is very complex. Highly condensed chromatin and huge numbers of components, such as transcription factors, chromatin proteins and RNA-processing factors, cram together in a very small volume. Essential nuclear processes such as transcription, replication, and repair occur at spatially defined locations in the nucleus. Accumulating evidence suggests that the expression of many genes is correlated with their positions in cell nucleus, and the spatial organization of chromatins has played essential role in regulating transcriptional activity [1]. How these could be done is one of the greatest challenges in molecular biology. 1 DNA helix is hierarchically packaged into chromatin in an elegant way, and eventually form a chromosome in the eukaryotic nucleus over several levels of higher-order structures [1], indicating that a range of microscopy techniques with spatial and temporal scales that cover several orders of magnitude are necessary to understand the organization principles at different levels in a chromosome. For example, the structure of nucleosomes, the fundamental organization unit of chromatin, has been elucidated by X-ray crystals at nanometer scale [2]. The structure of "beads-on-a-string" fiber, which has a diameter of 11-nm and is the very first level of chromatin organization, is also well-understood through Electron Microscope [33]. However, substructure at the scale of 10-200 nm is poorly understood, especially in live cells, partly due to the requirement of biological system that the dynamics, process and function in biology need to be measured with high spatial (approximately nanometer) and temporal (approximately microsecond to millisecond) † These authors contributed equally to this work.

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Rapid chromosome territory relocation by nuclear motor activity in response to serum removal in primary human fibroblasts

Abstract: Nuclear myosin 1β-dependent repositioning of chromosome territories occurs within 15 minutes of serum starvation in human cells.

Cited by 167 publications

References 68 publications

Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

Topologically associated domains enriched for lineage-specific genes reveal expression-dependent nuclear topologies during myogenesis

Active maintenance of nuclear actin by importin 9 supports transcription

Developing bioimaging and quantitative methods to study 3D genome

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